Gastric vascular actions of prostanoids and the dual effect of arachidonic acid.
The effects of several prostanoids and arachidonic acid on gastric vascular perfusion pressure were studied in dogs. A chambered segment of gastric fundus in anesthetized, heparin-treated dogs was perfused at constant flow (10 ml.min-1) with femoral arterial blood. Changes in perfusion pressure were measured after intra-arterial injection of each agent, at a point from which it reached the stomach in 3 s. Prostacyclin, prostaglandin E2 (PGE2), and PGE1 (5-40 ng) reduced perfusion pressure by 10-35 mmHg and were equipotent. 6-oxo-PGE1, the endoperoxide PGH2, and two stable prostacyclin analogues carbacyclin and 6 beta-PGI1 were less potent vasodilators, whereas 6-oxo-PGF1a was inactive. The epoxymethano endoperoxide analogues (U-46619 and U-44069) were equipotent vasoconstrictors, doses of 10-100 ng causing increases in perfusion pressure of 10-35 mmHg. PGF2a and noradrenaline also had vasoconstrictor actions. PGD2 had inconsistent actions. The effect of arachidonic acid on perfusion pressure varied with the length of time in contact with blood. Close (3 s incubation) intra-arterial injection (25-200 micrograms) produced vasodilation, whereas distal intra-arterial injection, which allowed 30 s of contact with blood before reaching the stomach, produced vasoconstriction as evidenced by dose-related increases in perfusion pressure (10-65 mmHg). These observations suggest that arachidonic acid, given by close intraarterial injection, is converted in the stomach mainly to vasodilator substances, presumably PGI2 or PGE2, but is converted mainly to a vasoconstrictor substance, presumably thromboxane A2, when allowed to mix with blood for 30 s.
D000244:Adenosine Diphosphate / Q000097:blood; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010477:Perfusion; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000494:pharmacology*; D012701:Serotonin / Q000097:blood; D013270:Stomach / Q000098:blood supply*; D014661:Vasoconstriction / Q000187:drug effects*; D014664:Vasodilation / Q000187:drug effects*
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D012701:Serotonin; D000244:Adenosine Diphosphate; D009638:Norepinephrine; D007213:Indomethacin